Preparation of 1-(carbamoyl)-n-(carbamoyloxy) thioformimidates from alkyl acetoacetates

ABSTRACT

1-(CARBAMOYL)-N-(CARBAMOYLOXY)THIOFORMIMIDATES SUCH AS METHYL 1-(CARBAMOYL)-N-(METHYLCARBAMOXYLOXY) THIOFORMIMIDATE AND METHYL 1-(DIMETHYLCARBAMOYL)-N(METHYLCARBAMOYLOXY)THIOFORMIMIDATE ARE PREPARED BY THE STEPS OF (A) REACTING AN ALKYL ACETOCETATE WITH NITROUS ACID PRODUCED IN SITU, IN THE PRESENCE OF WATER OR ALCOHOL: (B) CHLORINATING THE PRODUCT OF (A) AFTER COOLING TO -10 TO 40*C; (C) REACTING THE HYDROXAMOYL CHLORIDE FORMED IN (B) WITH AN ALKYL MERCAPTAN AND THEN ADDING A BASE; (D) REACTING THE PRODUCT OF (C) WITH AMMONIA OR AN AMINE IN THE PRESENCE OF WATER OR AN ALCOHOL; AND (E) REACTING THE PRODUCT OF (D) WITH EITHER (1) A CARBAMOYL CHLORIDE, OPTIONALLY IN THE PRESENCE OF A BASE; OR (2) AN INSOCYANATE, OPTIONALLY IN THE PRESENCE OF A BASIC CATALYST, IN WATER OR ORGANIC SOLVENTS SUCH AS ACETONE AND METHYLENE CHLORIDE.

United States Patent O 3,560,555 PREPARATION OF 1-(CARBAMOYL)-N-(CAR- BAMOYLOXY)THIOFORMIMIDATES FROM ALKYL ACETOACETATES Julius J. Fuchs, Wilmington, Del., assignor to E. I. du Pont de Nemours and Company, Wilmington, Del., a corporation of Delaware No Drawing. Filed Dec. 27, 1968, Ser. No. 787,592 Int. Cl. C07c 161/00 US. Cl. 260-482 16 Claims ABSTRACT OF THE DISCLOSURE 1- (carbamoyl) N (carbamoyloxy)thioformimidates such as methyl l-(carbamoyl)-N-(methylcarbamoxyloxy) thioformimidate and methyl 1-(dimethylcarbamoyl)-N- (methylcarbamoyloxy)thioformimidate are prepared by the steps of (a) reacting an alkyl acetocetate with nitrous acid produced in situ, in the presence of water or alcohol;

,(b) chlorinating the product of (a) after cooling to (c) reacting the hydroxamoyl chloride formed in (b) with an alkyl mercaptan and then adding a base;

(d) reacting the product of (c) with ammonia or an amine in the presence of Water or an alcohol; and

(e) reacting the product of (d) with either (1) a carbamoyl chloride, optionally in the presence of a base; or

(2) an isocyanate, optionally in the presence of a basic catalyst, in water or organic sol-vents such as acetone and methylene chloride.

BACKGROUND OF THE INVENTION This invention relates to methods for preparing 1- carbamoyl -'N- (carb-amoyloxy) thioformimidates. More particularly, this invention is directed to methods of preparing the thioformimidates by reacting an alkyl acetoacetate with nitrous acid, chlorinating that reaction product, reacting the resultant hydroxamoyl chloride with an alkyl mercaptan in the presence of a base, then aminating, and then preparing the desired thioformimidates by reaction with either a suitable carbamoyl chloride or isocyanate optionally in the presence of a base.

The product thioformimidates are useful as pesticides and can be prepared in the manner disclosed in copending application Ser. No. 728,739, filed May 13, 1968. They can also be prepared from glyoxylic acid in the manner disclosed and claimed in copending application Ser. No. 772,811 filed Nov. 1, 1968.

By the methods of this invention it is possible to prepare the thioformimidates of Formula 1 below in a fivestep process in which the first three steps can be operatively combined. By thus avoiding the necessity to separate and recover intermediate compounds the methods of this invention permit economic preparation of the compounds of Formula 1 below in outstanding yield.

SUMMARY This invention is directed to the preparation of alkyl l-(carbamoyl) N (carbamoyloxy) thioforrnimidates of the following formula R is alkyl of 1 through 4 carbon atoms or alkenyl of 3 through 4 carbon atoms; R; is hydrogen, alkyl of 1 through 4 carbon atoms, alkenyl tit of 3 through 4 carbon atoms, methoxy, or cycloalkyl of 3 through 5 carbon atoms;

R is hydrogen, alkyl or 1 through 4 carbon atoms or alkenyl of 3 through 4 carbon atoms; with the proviso that R and R can be joined and are alkylene of 2 through 6 carbon atoms, and with the limitation that R and R never total more than 7 carbon atoms;

R, is alkyl of 1 through 3 carbon atoms, allyl or propargyl; and

R is hydrogen or methyl;

by the steps comprising:

(a) reacting an alkyl acetoacetate with nitrous acid produced in situ, in the presence of Water, methanol, ethanol, isopropanol or their mixtures;

,(b) cooling the product of (a) to 10 to 40 C. and

chlorinating;

(c) reacting the product of (b) with an alkyl mercaptan then adding base to the reaction mixture;

(d) aminating the product of (c) with 2 moles of ammonia or an amine in the presence of water or alcohol; and

(e) reacting the product of (d) with a carbamoyl chloride or an isocyanate in Water, acetone, methylene chloride, methyl ethyl ketone, or methyl isobutyl ketone in the presence or absence of a base,

The compounds of Formula 1 and their use as pesticides are described and exemplified in application Ser. No. 728,739, referred to above.

DESCRIPTION OF THE INVENTION The process of this invention used in preparing the compounds of Formula 1 comprises the five steps enumerated above, and more fully described as follows:

Step (a) in which R is methyl, ethyl or isopropyl, and R is hydrogen, methyl, ethyl or isopropyl.

The alkyl acetoacetate and solvent are charged initially to the reaction vessel. The source of nitrous acid is then added as rapidly as is convenient, either as a solid or in solution. If an acid is to be used to generate nitrous acid it is then added to the reaction mixture with agitation. The acid is added at such a rate that the temperature remains between -10 and 50 C. and preferably between 0 and 30 C. The addition rate of the acid is also controlled so that the pH of the reaction mixture does not go below 4.0 and preferably not below 4.5. If the acid is added at a rate so rapid that the pH and temperature control are not maintained, nitrous acid may be liberated too rapidly and enter into undesirable side reactions.

Water, methanol, ethanol, isopropanol and their mixtures are suitable solvents. Of these, water is generally the preferred solvent for reasons of economy and solubility. However, when isopropyl acetoacetate is used it is preferred to use an alcohol as a solvent to increase the solubility of the acetoacetate and facilitate its reaction.

Suitable sources of nitrous acid are dinitrogen trioxide; alkyl nitrites; and sodium nitrite, potassium nitrite and calcium nitrite in conjunction with a generating acid such as hydrochloric, sulfuric and acetic. Of these sodium nitrite in conjunction with hydrochloric acid is the preferred source of nitrous acid because of convenience and economy, and ease of handling the by-product sodium chloride.

Of the alkyl acetoacetates the methyl and ethyl esters are preferred because of their high water-solubility and low cost. Of these two, the methyl ester is most preferred.

As stated above, water is the preferred solvent and it is preferred to use water in an amount of about 0.4 liter per mole of alkyl acetoacetate. Thus when sodium nitrite and hydrochloric acid, the preferred source of nitrous acid, are used to generate nitrous acid the sodium chloride by-product remains in solution, facilitating handling of the reaction mixture.

The source of nitrous acid is used in stoichiometric amounts based on the alkyl acetoacetate. Greater or lesser amounts can be used but only at an economic disadvantage.

The generating acid when used is used in stoichiometric amounts based on the source of nitrous acid. Use of amounts greater or less than stoichiometric results in waste of one of the reactants.

If desired the product of step (a) can be isolated such as by extraction with a water-immiscible organic solvent followed by evaporation of the solvent. Methylene chloride is a suitable water-immiscible solvent. It is usually preferred to proceed directly to step (b) without isolating the product of step (a).

Step (b) NOII C) IEIOII (Iii) wherein R and R are as defined in step (a).

If the oxime ester of step (a) has been isolated or purified, it is preferred to mix the ester with water, cool the mixture and add chlorine. If the ester has not been isolated from the reaction medium of step (a) the product mixture is cooled and chlorinated without adding water.

The chlorination is carried out at a temperature between about C. and C. and preferably between +10 C. and 30 C. The amount of chlorine used will vary from stoichiometric to 5% molar excess but it is preferred to use stoichiometric amounts.

The chlorine is ordinarily added over a period of 30 to minutes although it can be added more rapidly if desired. After addition is complete the mixture is stirred, usually for about 30 to minutes, at a temperature of about 20 C. The reaction is complete when the color of the reaction mixture has disappeared.

Elemental chlorine is preferred as the source of chlorine for economic reasons, however other chlorinating agents, such as sulfuryl chloride, can be used if desired.

The product of step (b) can be isolated such as by filtration or extraction but it is usually preferred to go directly to step (c) without isolating the product of step (b).

Suitable solvents include water, methanol, ethanol, isopropanol and their mixtures. For economic reasons and to avoid side-reactions of chlorine with an alcohol, water is the preferred solvent and obviously when step (a) product is used without isolating the product from the solvent, step (b) is carried out in the solvent of step (a).

Step (c) The hydroxamoyl chloride from step (b) is reacted with an alkyl mercaptan in a solvent and then the pH is raised by addition of a base according to the equation wherein R, R' and R are as defined above.

For best yields the reaction product of step (b) is cooled to below 20 C. prior to addition of the mercaptan. A temperature range of 0 to l0 C. is most preferred.

Bases suitable for adjusting the pH are the hydroxides, carbonates and bicarbonates of sodium, potassium, calcium and magnesium. The final pH should be between 5 and 9 and a pH of about 7 is preferred.

The product can be isolated if desired by conventional techniques such as filtration, solvent extraction or distillation. Alternatively, the product mixture can be used as is in step ((1).

Step (d) The product of step (c) is reacted with an amine in the presence of water, methanol, ethanol, isopropanol or their mixtures according to the equation 0 NOH wherein R, R, R R and R are as defined above.

If the product of step (c) was isolated it is first dispersed with stirring in the solvent medium, preferably in one of the alcohols or an alcohol-water mixture.

To this mixture is added approximately 2 moles of ammonia, or a primary or secondary amine. A tertiary amine such as trimethylamine can be substituted for one mole of these amines with about the same results. Two moles of amine are necessary because one mole forms a salt with the oxime function while another mole participates directly in the reaction.

The product of step (d) can be isolated in a conventional manner such as by filtration or evaporation of the solvent. It is desirable to isolate this product or at least to remove any excess ammonia or amine, prior to performing the reaction of step (e).

Step (e) Conversion of the product of step (d) to the oxime carbarnate is carried out by reacting the product of step (d) with an isocyanate or a carbamoyl chloride according to the equation wherein R R R and R are as defined above, or

wherein R R R R and R are as defined above.

The reactions of step (e) are carried out in a solvent such as water, acetone, methyl ethyl ketone, methyl isobutyl ketone, or methylene chloride, at a temperature which can range from below 10 C. to the boiling point of the solvent. An anhydrous solvent is preferred since isocyanates and carbamoyl chlorides can react with water. The reaction of step (e is facilitated by the presence of a basic catalyst such as trimethylamine or triethylenediamine. The reaction of step (e is advantageously carried out in the presence of a base such as triethylamine,

trimethylamine or the hydroxides, carbonates bicarbonates stable pH of 7 is obtained. The resulting reaction mass of sodium, potassium, calcium or magnesium. is then extracted with methlyene chloride, followed by Alternatively, the sodium salt of the product of step evaporation of the methylene chloride under vacuum. (d) can be formed by reaction with a metal hydride such The resulting residue consisting of crude methyl l-methas sodium hydride. The resulting sodium salt can then be oxycarbonyl-N-hydroxythioformimidate, is then dissolved reacted with a carbamoyl chloride in an inert solvent in 200 parts of methanol and 100 parts of anhydrous such as tetrahydrofuran to obtain products as obtained in dimethylamine are dissolved in the solution at a temthe (c reaction. perature below 30 C. This solution'is allowed to stand The alkyl 1 (carbamoyl)-N-(carbamoyl)thioformat ambient temperatures overnight. Removal of excess imidate products of step (e) can be isolated by condimethylamine and the solvent under reduced pressure ventional procedures such as filtration or extraction. leaves 106 parts (66% of theory) of methyl l-(dimethyl- Of the steps (a) through (e) the more important are carbamoyl)-N-hydroxythioformimidate, melting point steps (a) and (b) and the most important is step (b) 183-184" C. which provides an advantageous method of preparing the To a suspension of 70 parts of methyl l-(dimethylcarhydroxamoyl chloride. One preferred sequence of rebamoyl)-N-hydroxythioformimidate and /2 part of triactions is to chlorinate in a step (b) reaction apreviously ethylenediamine in 350 parts of acetone at 40 C. is obtained ester, prepared by any suitable process, and added slowly 27 parts of methyl isocyanate. The temfollow this chlorination with the steps (c), (d) and (e). perature of the reaction mass rises to 58 C. during the The process of this invention is further illustrated in addition. After the temperature of the reaction mass has the following examples wherein parts and percentages are subsided to 25 C., the solvent is evaporated under reby weight unless otherwise noted. duced pressure, and the resulting residue crystallized. Re-

crystallization from benzene gives an isomer of methyl EXAMPLE 1 l-(dirnethylcarbamoyl) N (methylcarbamoyloxy) thioformimidate, melting point 109-110" C. Recrystallization To a solution of 116.1 parts of methyl acetoacetate from water gives the other isomer of methyl l-(dimethyland 70 parts of sodium nitrite in 400 parts of water at carbamoyl)-N (methylcarbamoyloxy)thioforrnimidate, C. kept under a nitrogen atmosphere, is added gradualmelting point 101103 0.

1y 100 parts of 36% aqueous hydrochloric acid so that Similar results are obtained in the above example by the pH of the solution remains above 4.5. The resulting substituting equivalent amounts of ethyl acetoacetate or two-phase reaction mixture is then cooled to 20 C. isopropyl acetoacetate for the methyl acetoacetate. Likeand 72 parts of chlorine are added at 20 C. in 30-45 30 wise equivalent quantities of potassium nitrite or calcium minutes. When the chlorine has all been added, the twonitrite can be substituted for the sodium nitrite in Examphase reaction mixture is agitated for /2 hour at 20 C. ple I.

The reaction mixture is then cooled to 10 C. and 55 The compounds of Table I are prepared by the proparts of methyl mercaptan are added, followed by the cedures of Example I, usng the mercaptans, amines and gradual addition of 240 parts of 50% aqueous sodium isocyanates listed in place of the methyl mercaptan, dihydroxide solution at ---10 to -5 C., at which time a methylamine and methyl isocyanate of Example I.

TABLE I Mercaptan Amine Isoeyanate Product Ethyl mercaptan Dimethylamine Methyl isocyanate Eglliggel-dirnethylearbamoyl-N-(methylcarbamoyloxy) thioformim- Allyl mereaptan do do Allyl l-dimethylearbamoyl-N-(methylearbamoyloxy)thioformimi- But-2-enyl mercaptan -do Ethyl isocyanate Bpi-iinyl l-dimethylcarbamoyl-N-(ethylcarbamoyloxy)thiolormim- Isopropyl mercaptan do Allyl isocyanate Isgggggyl l-dimethylearbamoyl N-(allylcarbamoyloxy)thiolormim- Methyl mercaptan do Propargyl isocyanate Mrlaltrlliiyllaldimethylcarbamoyl-N-(propargylcarbamoyloxy)thioform- Propyl mercaptan do Methyl isocyanate.--" Pliggyel'l-dimethylcarbamoyl-N-(methylcarbamoyloxy)thiotormim- Allyl mercaptan do Allyl isocyanate Allyl l-dimethylcarbamoyl-N-(allylearbamoyloxy)thiofonnimidate. Isopropyl mercaptan do Methyl isocyanate"--. lsgplli'ggytlll-dimethylcarbamoyl-N-(methylcarbamoyloxy)thiotorm- Butyl mercaptan do do Bugglel-dimethy1carbamoyl-N-(methylcarbamoyloxy)thioformim- Sec-Butyl mercaptan do ..do secigliulglel-dimethylcarbamoyl-N-(methylcarbamoyloxy)thioiorrntert-Butyl mercaptan do do mgr-$38321. l-dimethylearbamoyl-N-(methylcarbamoyloxy) thioform- Methyl mercaptan do Ethyl isocyanate Meltggl l-dimethylcarbamoyl-N-(ethylearbamoyloxy)thioformimi- Butyl mercaptan do do B151g:.l-dimethylcarbamoyl-N-(ethylearbamoyloxy) thioformirni- Methyl mercaptan do Isopropyl isocyanate- MtieItrllriylnlt-sdimethylcarbamoyl-N-(isopropylearbamoyloxy) thioiorm- Butyl mercaptan do do Bpiglet-dimethylcarbamoyl-N-(isopropylcarbamoyloxy)thioformim- Allyl mercaptan Propyl isocyanate Alglel-dimethylcarbamoyl-N-(propylearbamoyloxy)thioformimi- Methyl mereaptan Allyl isoeyanate Meiglgll l-dimethylcarbamoyl-N-(allylcarbamoyloxy) thioformimi- Bu yl mercaptan do do Buitggl-dimethylcarbamoyl-N-(allylcarbamoyloxy) thioiormimi- Allyl mercaptan do Propargyl isocyanate.- Allygttdimethylcarbamoyl N (propargylcarbamoyloxy) thioformim- Methyl mercaptan Methylamine Methyl isocyanate Meghyel.l-(methylcarbamoyl)-N-(methylearbamoy1oxy)thioformim- Do Butylamine do Maggi 1-(butylcarbamoyl)-N-(methylcarbamoyloxy) thioformimi- Isopropy1rnereaptan Cyclopropylamine do lsgggpxylliggyelopropylcarbamoyl)-N-(methylcarbamoyloxy)thio- Allyl mercaptan N,O-dimethylhydroxylamine Ethyl isocyanate Allyl1-(N-methoxy-N-methylcarbamoyl)-N-(ethylcarbamoyloxy)- thioforrnimidate. Butyl mercaptan Allylamine do Butyl1-(allylcarbamoyl)-N-(ethylearbamoyloxy)thiololtmlmldate.

TABLE I. Continued Mercaptan Amine Isoeyzmate Product Methyl mercaptan Diallylaminc Allylisocyanate r Meltlyl1-(diallylcarbamoyl)-N-(allylcarbamoyloxy)thiotormimia e. Ethyl mercaptan Isopropylamiue tl Etlhyl l(isopropylcarbamoyl)-N-(allylcai'bamoyloxy)thioiormimia e. Methylmereaptan Ethylamine Propargylisocyanaten Mehyl l-(ethylcarbamoyl)-N-(propargylearbamoyloxy)thiol'ol'mimi ate. D0 Diethylamine Methyl isocyanate Meghyl l-(dicthylcarbamoyl)-N-(methylcarbamoyloxy)thioformimi ate. Do Diisopropylamine ..do Methyl 1-(diisopropylearbamoyl)-N-(methylearbamoyloxy)thiotormimidatc. Ethyl mcrcaptan But-2-cnylamiue Isopropyl isocyanatm- Ethyl 1-(but-2-enylearbamoyl)-N-isopropylcarbamoyloxy)tluotorm- 1m .e. Methyl mereaptan Aziridinc Methyl isocyanatc"... Mectlhyl l-(aziridinoearbonyl)-N-(mcthylcarbamoyloxy)thiol'orrnimi ate. Do Hexahydroazepine do Methyl 1-(hexahydroazepinocarbonyl)-N-(methylcarbarnoyloxy)- thioformimidate. I Do Iyrrolidine .d0 Methgl1-(pyrrolidinocarbonyl)-N-(methylearbamoyloxy)thiotonm imi ate. D0 Hethylamine Allyl isocyanate Meithyl l-(methylcarbamoyl)-N-(allylearbamoyl0xy)thiolormimiate. Do Allylamine Propm'gyl is0cyanato. Methyl l(ullylearbam0yl)-N-(propargylearbamoyloxy)thiolormimi( ate. Do N,O-dimethylhydroxylamine. Methyl is0cyanate Methyl l-(N-metlxy-N-methylearbamoyl)-N-(methylcarbamoyl- 0xy)thiot0rmimidate. Do N-methyl-N-e hylamine Allyl isocyanatc Methyl l-(N-methyl-N-ethylearbam0yl)-N-(allylearbamoyloxy)- thioformimidate. Ethyl mercaptan Pipcridinc d0 E313? l-(piperidinoearbonyl)-N-(allylearbamoyloxy)thiol'ormimia e. D0 ..d0 Butylisocyanate Ethyl1-(piperidinocarbonyl)-N-(butylearbamoyloxy)thietormimiate. Butyl mercaptan d0 Methyl isocyanate l Bugyl l-(pipei'idinocarbouyl)-N-(mothylcarbamoyloxy)thiolormiml a e. Do ..d0 Butyl isocyanate Butyl l-(pipcridinoenrbonyl)-N-(butylearbamoyloxy)thiol'ormimi- 1 ate. Methyl mercaptan Nanethyl-N-butylamine Methyl isocyanatem Melthyl1-(N-rgethyl-N-butylcarbamoyl)-N-(methy1carbamoyloxy)- t llO ormimi a 0. D0 N-methyl-N-allylamine (l0 Methyl l-(N-methyl-N-allylearbamoyl)-N-(metliylearbumoyloxy)- thiotormimidate.

EXAMPLE H EXAMPLE III Crude methyl 1-methoxycarbonyl-N-hydroxythioformimidate obtained as in Example I above, is dissolved in 200 parts of concentrated aqueous ammonia at a temperature below C. The solution is allowed to stand overnight. After removal of a small amount of undissolved material by filtration, the filtrate is concentrated under reduced pressure to give 105 parts of methyl l-(carbamoyl)-N-hydroxythioformimidate, melting point 163- 164 C.

To a suspension of 400 parts of methyl 1-(carbamoyl)- N-hydroxythioformimidate and 1 part of triethylenediamine in 2000 parts of acetone at C. are added slowly 171 parts of methyl isocyanate. The temperature of the reaction mixture rises to 58 C. during the addition and then subsides to 25 C. At this point the reaction mass is cooled to 0 C. and 547 parts of the product methyl lcarbamoyl -N- methylcarbamoyloxy) thioformimidate is filtered off. The product has a melting point of 161-165 C.

The compounds of Table II are prepared by the procedures of Examples I and II, using the mercaptans and isocyanates listed in place of methyl mercaptan and methyl isocyanate of Examples I and II.

To a solution of 116.1 parts of methyl acetoacetate and 70 parts of sodium nitrite in 400 parts of water at 30 C., which is kept under a nitrogen blanket, is gradually added 100 parts of 36% aqueous hydrochloric acid so that the pH of the solution remains above 4.5. The resulting two-phase reaction mixture is then cooled to 20 C. and 72 parts of chlorine added at 20 C. within 30-45 minutes. When the chlorine has all been added, the twophase reaction mixture is agitated for /2 hour, at the end of which it has become colorless. The reaction mixture is then cooled to 10 C. and parts of methyl mercaptan added, followed by the gradual addition of 240 parts of 50% aqueous sodium hydroxide solution at 10 to 5 C. until a stable pH of 7 is obtained. The resulting reaction mass is then extracted with methylene chloride. Evaporation of the solvent under reduced pressure leaves 137 parts of crude 1-(methoxycarbonyl)-N-hydroxythioformimidate, which is purified by recrystallization from benzene to give pure material with a melting point of 63-64 C.

EXAMPLE IV To a solution of 116.1 parts of methyl acetoacetate and parts of sodium nitrite in 400 parts of water at TABLE II l\lercaptan Isocyanate Product;

Ethyl mercaptan Methyl isoeyanate. Ethyl l-earbamoyl-N-(methylcarbamoyloxy)thiotormimidate. Allyl mercaptan d0 Allyl lcarbamoyl-N-(me hylcarbamoyloxy)thiotormimidate. But-2ei1yl mereaptal Ethyl isoeyanate.-- But-Z-enyl l-carbamoyl-N-(ethylcarbamoyloxy)thiotormimidate. IsopropylmereaptmL Allyl isocyanate Isopropyl l-earbamoyl-N-(allylearbamoyloxy)thiotormimidate. Methyl mereaptam Propargyl isoeyanate Methyl l-earbamoyl-N-(propargylcarbamoyloxy) thioformimidate. Propyl mercaptan Methyl isoeyanate Propyl l-earbamoyl-N-(methylcarbamoyloxy)thiolormimidate. Allyl mereaptam. Allyl lsoeyanate Allyl l-carbamoyl-N-(allylcarbamoyloxy)thiotormimidate. Isopropyl mercapta Methyl isoeyanate Isopropyl l-carbamoyl-N-(methylcarbamoyloxy)thiol'ormimidate. Butyl mereaptan. do Butyl l-carbam0yl-N-(methylcarbamoyloxy) thiotormimidate. sec-Butyl mereaptan do sec-Butyl l-carbamoyl-N-(methylcarbamoyloxy)thioformimidate, te1t-Buty1mercaptan do tert-Butyl l-earbamoyl-N-(methylearbamoyloxy)thioformimldate. Methyl mereaptam. Ethyl isocyanate Methyl l-earbamoyl-N-(ethylcarbamoylox )thiotormimidate. Butyl mel'captan do Butyl l-carbamoyl-N-(ethylearbamoyloxy thioformimidate. Methyl mercaptan. Isopropyl isoeyanate Methyl l-carbamoyl-N-(isopropylcarbamoyloxy)thioformimidate. Butyl mereaptan. do Butyl 1-carl amoyl-N-(isopropylcarbamoyloxy)thiotormimidate. Allylmcrcaptan. .do. Allyl l-carbamoyl-N-(isopropylearbamoyloxy)thioformimidate.

Do Propyl lsoeyauate Allyl l-carbamoyl-N-(propylcarbamoyloxy) thiolorrnimidate. Methyl mercaptan. Allyl isoeyanate Methyl l earbamoyl-N-(allylcarbamoyloxy)thioformimidate. Butyl mereaptan. do Butyl l-carbamoyl-N-(allylcarbamoyloxy)thioformimidate.

Allyl mercaptan Propargyl isoeyanate Allyl l-carbamoyl-N-(propargylcarbamoyloxy) thiotormimidate.

30 C. under a nitrogen blanket, is gradually added 100 oxy)thioformimidate is recovered by removal of the parts of 36%! aqueous hydrochloric acid so that the pH solvent under reduced pressure. of the solution remains above 4.5. A yellow two-phase The compounds of Table III are prepared according reaction mixture of methyl acetoacetate oxime and water to the procedures of Example VI, using the N-hydroxyis formed; the product can be separated by decantation thioformimidates and carbamoyl chlorides listed in place or extraction with methylene chloride, and can be puri- 5 of methyl l-(carbamoyl)-N-hydroxythioformimidate and fied by distillation at 8286 C./ 0.15 mm., or by crystaldimethylcarbamoyl chloride.

TABLE III N-hydl'oxythioformimldate Carbamoyl chloride Product Methyl l-carbalnoyl-N-hydroxythioiol'mimidate N-allyl-N-methylcarbamoyl chloride Methyl l-earbamoyl-N-(N-allyl-N-methylcarbamoyloxy)thiot'ormimidate. D0 N-methyl-N-propargylcarbamoyl chloride. Methyl 1-carbam0yl-N-(N-methyl-N-propargylcal'bamoyloxy) thiolol'mimi date. Do N-methyl-N-propylearbarnoyl ehl0ride Methyl l-earbamoyl-N-(N-methyl N-propylearbarnoyloxy) thiof ormixni date. Do... N-ethyl-N-methylcarbamoylchloride methyl Lcarbamoyl-N-(-Nethyl-N-methylcarbamoyloxy) thio formimidate. Methyl l-methylcalbaInoyl-N-hydroxythioiormimidatm Dimethylcarbamoyl chloride Methyl l-(methylcarbarnoyl)-N-(dimethy1carbamoyloxy) thioformimidate. Methyl 1-dimethylcarbamoyl-N-hydroxythioionnimidate do Methyl 1-(dimethylcarbamoylyN-(dimethylcarbamoyloxy)thioiol'rnimidate. Methyl l-eyelopentylcarbamoyl-N-hydroxythioforrnimido Methyl l-(eyclopentylearbamoyl)-N-(dimethdate. ylcarbamoyloxy) thioformimida te. Propyl l-carbamoyl-N-hydroxythioformimidata do Propyl l-calvamoyl-N-(dimethylearbamoyl l oxy)thioformimidate. Ethyl l-earbamoyl-N-hydroxythioiormimidate do Ethyl l earbamoyl-N-(dimethylcarbamoyloxy)thioiormimidate. Butyl l-carbamoyl-N-hydroxythioiormimidate do Butyl l-carbamoyl-N-(dimethylcarbamoyloxy) thioformimidate. Methyl I-piperdinocarbonyl-N-hydroxythioiormimidate "do Methyl l-piperidinocarbonyl-N-(dimethylcarbamoyloxy)thioformirnidate. Allyl l-carbamoyl-N-(dimethylcarbamoyloxy) thioiormimidate. But-2-enyl l-carbanloyl-N-hydroxythiofonnimidate do But-2enyl l-earbamoyl-N-(dimethylcarbamoyloxy) thiofornlimidate.

Allyl l-earbamoyl-N-hydroxythioformimidate lization from carbon tetrachloride. The product has a 30 I claim:

melting point of 3437 C. 1. A process for preparing 1-(carbamoyl)-N-carbam- The yellow two-phase reaction mixture of methyl acetooyloxy)thioformimidates of the formula acetate oxime obtained above is treated after cooling R3 0 0 R4 to C. with 72 parts of chlorine within -45 minutes. II II The two-phase reaction mixture becomes darker at the (1) /N CC=N 0"CTN start of the chlorination, but the color becomes lighter 2 r R5 as the chlorination progresses. When all of the chlorine wherein has been added, the two-phase reaction mixture is agitated at 20 C. for /2 hour, at the end of which a colorless i gi i g gggg fg g f atoms or alkenyl of reaction mixture has resulted. The mixture 18 extracted R2 is ydrogen, alkyl of 1 through 4 carbon atoms, alkenyl wlth methylene chloride. After evaporation of the methylof 3 through 4 carbon atoms methoxy or cycloalkyl ene chloride there is obtained 125 parts of oily, crude of 3 through 5 carbon atoms. 1-(methoxycarbonyl)formhydroxamoyl chloride, which R3 is hydrogen alkyl of 1 through 4 carbon atoms or crystallizes when cooled. Recrystallization from benzene alkenyl of 3 through 4 carbon atoms; with the proviso glves pure L methoxycarbonyb formhydroxamoyl ch10 that R and R can be taken together and are alkylene ride with a melting point of 63*650 of 2 through 6 carbon atoms, and with the limitation EXAMPLE V that R and R never total more than 7 carbon atoms; To a solution of 72.5 parts of distilled methyl aceto- R4 is alkyl of 1 through 3 carbon atoms anyl or pargyl; and

acetate oxlme m 200 parts of water 1s added within 30 R5 is hydrogen or methyl;

minutes 36 parts of chlorine at 15-20 C. Immediately on introduction of the chlorine, the solution becomes y the Steps comprising brown, but the color gradually turns to yellow with reactingmethyl, y or p py acetoacetate the precipitation of an oil. When all of the chlorine has With nitrous acid Produced in Situ, in the Presence been added, the reaction mixture is agitated until it beof Water, methanol, n isopropanol their comes colorless, which occurs within hour at 20 C. mixtures;

Extraction with methylene chloride, drying of the solu- Cooling the Product of p to a temperature tion with calcium chloride and evaporation of the solvent of from about t0 and ehlolihatihg the gives parts f il crude l eth xy arb y)f cooled product 1n the presence of water, methanol, hydroxamoyl chloride, which contains small amounts of ethanol; lsopropahol or the"? mlXtllfeS;

acetic acid. The crude product crystallizes when cooled, 60 l'eaetlhg the Product of Step Wlth an alkyl and can be purified by recrystallization from benzene to mercaptan of the formula give pure l-(methoxycarbonyl)formhydroxamoyl chlo- R SH nde wlth meltmg point of 63 65 wherein R is as defined above; and then raising EXAMPLE VI 5 the pH to the range of 5-9 by the addition of a To a stirred suspension of 48 parts of 50% sodium hydrmfldei carhonate or blc'flrbonate of Sodlum: hydride and mineral oil in 648 parts of tetrahydrofuran P g calclum magtfeslumi is added in portions, over a one-hour period, 114 parts amlhatlhg the Product OI p YVlth aheut 2 of methyl 1 (carbamoyl) N hydroxythioformimidate. motes P mole of Product ahlmonla, Prlmary The temperature is maintained at 20 to 30 C. After subamlhe or a Secondary afhlne 111 the p h P sidence of hydrogen evolution, 107.5 parts of dimethyl- Water, methanol, ethanol, ISOPIOPaHOI their IIllX- carbamoyl chloride is added dropwise at 15-25 C. Stirthree; and ring is continued for one hour after the completion of the reacting the Product Of p Wlth an PP addition. The inorganic solids are then removed by filtrapriate isocyanate or carbamoyl chloride in the prestion and the methyl l-carbamoyl-N-(dimethylcarbamoylonce of water, acetone, methylene chloride, methyl 1 1 ethyl ketone, or methyl isobutyl ketone and in the presence or absence of a base.

2. The process of claim 1 wherein the amination is carried out with ammonia.

3. The process of claim 1 wherein amination is carried out with dimethylamine.

4. The process of claim 1 wherein step (a) is carried out in water, using sodium nitrite and hydrochloric acid as the source of nitrous acid.

5. The process of claim 1 wherein step (b) is carried out at a temperature between C. and 30 C.

6. The process of claim 1 wherein step (c) is carried out after cooling to a temperature below C.

7. The process of claim 1 wherein step (d) is carried out in methanol, ethanol, isopropanol or their mixtures with water.

8. The process of claim 1 wherein excess ammonia or amine are removed after step (d) and prior to step (e).

9. The process of claim 1 wherein step (e) is carried out using an isocyanate and trimethylamine or triethylenediamine as the basic catalyst.

10. The process of claim 1 wherein step (e) is carried out using a carbamoyl chloride and triethylamine, trimethylamine, or a hydroxide, carbonate or bicarbonate of sodium, potassium, calcium or magnesium as the base.

11. A process for preparing hydroxamoyl chlorides of the formula wherein R is methyl, ethyl or isopropyl by the steps comprising (1) reacting methyl, ethyl, or isopropyl acetoacetate with nitrous acid produced in situ, at a temperature 12 between l0 and 50 C., and a pH above 4.0 in the presence of water, methanol, ethanol, isopropanol or their mixtures;

(2) cooling the product of step (1) to a temperature of from about 10 to C. and chlorinating the cooled product in the presence of water, methanol, ethanol, isopropanol or their mixtures.

12. The process of claim 11 wherein steps (1) and (2) are carried out in water.

13. The process of claim 11 wherein step (1) is carried out at a temperature between 0 C. and 30 C.

14. The process of claim 11 wherein step (1) is carried out at a pH above 4.5.

15. A process for chlorinating esters of acetoacetate oxime of the formula 0 N-OHO II I] ll ROCCCCH3 where R is methyl, ethyl or isopropyl comprising reacting the oxime with chlorine at a temperature between l0 and 40 C. in water, methanol, ethanol, isopropanol, or their mixtures, the chlorine being used in an amount approximately equal to stoichiometric.

16. The process of claim 15 wherein the reaction is carried out at a temperature between 10 C. and 30 C.

References Cited UNITED STATES PATENTS 3,256,330 6/1966 Kilsheimer et a1. 260-566A HENRY R. JILES, Primary Examiner S. D. WINTERS, Assistant Examiner US. Cl. X.R. 

